1. Description of the Invention
The present invention relates to certain novel 9-deoxy-9-methylene prostaglandins. More particularly, the present invention relates to 9-deoxy-9-methylene substituted derivatives of (dl)-11.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,18,19,20-tetranorprosta-4 ,5,13-(trans)-triene alcohols, aldehydes, and acids as well as the pharmaceutically acceptable, non-toxic lower alkyl esters and salts of the acid and the processes for preparing such compounds.
2. Related Art
Prostaglandin have classically been described as chemically related 20 carbon acid hydroxy fatty acids having the basic skeleton of prostanoic acids: ##STR2##
The prostaglandins having a hydroxyl group at the C-11 and a keto group at the C-9 position are known as the PGE series, those having an hydroxyl group in place of the keto group are known as the PGF series and are further designated by an .alpha. or .beta. suffix to indicate the configuration of the hydroxyl group at the said position. The natural compounds are the .alpha.-hydroxy substituted compounds. They may contain different degrees of unsaturation in the molecule, particularly at C-5, C-13 and C-17, the unsaturation is also indicated by a suffix. Thus, for example, the PGF.sub.1 and PGE.sub.1 series refer to prostanoic acid having a trans olefin bond at the C-13 position, while the PGF.sub.2 and PGE.sub.2 series refer to prostadienoic acids having a cis-olefin bond at the C-5 position and a trans olefin bond at the C-13 position. For a review on prostaglandins and the definition of primary prostaglandins, see for example, S. Bergstrom, Recent Progress in Hormone Research 22, pp. 153-175 (1966) and Science 157, p. 382 (1967) by the same author.
The preparation of derivatives of prostanoic acid has been extensive. The great majority of these studies have focused on modification of the two side chains, or modification of the substituents attached to the cyclopentane moiety. The synthesis of prostaglandin analogs having diethylenic (allenic) unsaturation in the carboxylic acid chain has been described in U.S. Pat. No. 3,879,438 issued to Crabbe and Fried. The synthesis of several prostaglandin analogs in which the alkyl chain attached to C-15 in the natural compound is replaced by an aryloxymethylene group has been reported in, for example, the U.S. Pat. Nos. 3,864,387, 3,954,881 and Belgium Pat. No. 806,995. Prostaglandins having 4,5-allenic unsaturation and 16-phenoxy and substituted 16-phenoxy-9-keto compounds are reported in U.S. Pat. No. 4,178,457 issued to Van Horn et al. Prostanoic acid derivatives having 9-deoxy-9-methylene-(trans)-2,3-didehydro-PGF.sub.1 are disclosed in U.S. Pat. No. 4,165,436. See also U.S. Pat. No. 4,296,256 which relates to 2-decarboxy-2-hydroxymethyl-19-keto-PG compounds.